SHARON NINA ADMONI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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- Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes(2020) SANTOS-BEZERRA, Daniele P.; FILGUEIRAS, Luciano R.; MONTEIRO, Maria Beatriz; ADMONI, Sharon N.; V, Ricardo Perez; CAVALEIRO, Ana M.; MACHADO, Cleide G.; MACHADO, Ubiratan F.; PASSARELLI, Marisa; JANCAR, Sonia; CORREA-GIANNELLA, Maria LuciaBackground and Aims. Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications. Methods and Results. Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA(1)C, of fructosamine, and of plasmatic LTB4. Conclusion. In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.
- Glutathione peroxidase 4 functional variant rs713041 modulates the risk for cardiovascular autonomic neuropathy in individuals with type 1 diabetes(2019) ADMONI, Sharon Nina; SANTOS-BEZERRA, Daniele Pereira; PEREZ, Ricardo Vesoni; PATENTE, Thiago Andrade; MONTEIRO, Maria Beatriz; CAVALEIRO, Ana Mercedes; PARISI, Maria Candida; NETO, Arnaldo Moura; PAVIN, Elizabeth Joao; QUEIROZ, Marcia Silva; NERY, Marcia; CORREA-GIANNELLA, Maria LuciaCardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the detoxification of peroxides and of reactive oxygen species. Thus, the association of a functional variant in the gene encoding glutathione peroxidase 4 (rs713041) with this diabetic complication was investigated in 341 individuals with type 1 diabetes evaluated for cardiac autonomic neuropathy status (61.7% women, 34 [27-42] years old; diabetes duration: 21 [15-27] years; HbA1c: 8.3% [7.4-9.4]; as median [interquartile interval]). Cardiac autonomic neuropathy was present in 29% of the participants. There was an inverse association of the minor T allele of rs713041 with cardiac autonomic neuropathy (odds ratio = 0.39; 95% confidence interval = 0.17-0.90; p = 0.0271) after adjustment for potential confounders. The functional glutathione peroxidase 4 variant rs713041 modulated the risk for cardiac autonomic neuropathy in the studied population with type 1 diabetes.
- Allelic variations in genes belonging to glutathione system increase proliferative retinopathy risk in type 1 diabetes individuals(2019) PEREZ, Ricardo Vessoni; MACHADO, Cleide Guimaraes; SANTOS-BEZERRA, Daniele Pereira; ADMONI, Sharon Nina; PATENTE, Thiago Andrade; MONTEIRO, Maria Beatriz; CAVALEIRO, Ana Mercedes; QUEIROZ, Marcia Silva; NERY, Marcia; CORREA-GIANNELLA, Maria LuciaAims: Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in regulatory regions of two genes belonging to the antioxidant glutathione (GSH) system: rs17883901 in GCLC and rs713041 in GPX4. Methods: A cross-sectional case-control study included 288 individuals (61% women, 34[+/- 11] years old, diabetes duration of 22[+/- 9] years, mean [+/- SD]) sorted according to DR stages: absence of DR (ADR), non proliferative DR (NPDR) and proliferative DR (PDR). SNPs were genotyped by real-time PCR using fluorescent labelled probes. Logistic regression models with adjustment for confounding covariates were employed. Results: The presence of at least one T-allele of rs17883901 in GCLC was an independent risk factor for PDR (OR 4.13, 95% CI 1.38-13.66, p = 0.014) in a polytomous regression model (PDR versus ADR). The presence of at least one T-allele of rs713041 in GPX4 conferred protection against PDR (OR 0.30, 95% CI 0.11-0.80, p = 0.017) in female T1D individuals. Conclusion: The functional SNPs rs17883901 and rs713041 modulate the risk for PDR in the studied population of T1D individuals, widening the spectrum of candidate genes for this complication.
- Distal Symmetric and Cardiovascular Autonomic Neuropathies in Brazilian Individuals with Type 2 Diabetes Followed in a Primary Health Care Unit: A Cross-Sectional Study(2020) MATOS, Mozania Reis de; SANTOS-BEZERRA, Daniele Pereira; CAVALCANTE, Cristiane das Gracas Dias; CARVALHO, Jacira Xavier de; LEITE, Juliana; NEVES, Jose Antonio Januario; ADMONI, Sharon Nina; PASSARELLI, Marisa; PARISI, Maria Candida; CORREA-GIANNELLA, Maria LuciaThe paucity of epidemiological data regarding diabetes complications in Brazil motivated us to evaluate the prevalence rates of distal symmetric polyneuropathy (DSP) and of cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes (T2D) followed in a primary care unit. A total of 551 individuals (59.3% women, 65 years old; diabetes duration of 10 years; HbA1c of 7.2%, medians) were included in this cross-sectional study. DSP was diagnosed by sum of the Neuropathy Symptoms Score (NSS) and Modified Neuropathy Disability Score (NDS) and by the Semmes-Weinstein monofilament. CAN was diagnosed by cardiovascular autonomic reflex tests combined with spectral analysis of heart rate variability. The prevalence rates of DSP were 6.3% and 14.3%, as evaluated by the sum of NSS and NDS and by the Semmes-Weinstein monofilament, respectively. Those with DSP diagnosed by monofilament presented longer diabetes duration, worse glycemic control and a higher stature. The prevalence rates of incipient and definitive CAN were 12.5% and 10%, respectively. Individuals with definitive CAN presented a higher frequency of hypercholesterolemia and of arterial hypertension. The higher prevalence rate of DSP with the use of the monofilament suggests that it may be a more appropriate tool to diagnose DSP in the primary care setting in Brazil.
- Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients(2018) SANTOS-BEZERRA, Daniele P.; MACHADO-LIMA, Adriana; MONTEIRO, Maria Beatriz; ADMONI, Sharon N.; PEREZ, Ricardo V.; MACHADO, Cleide G.; SHIMIZU, Maria Heloiza; CAVALEIRO, Ana M.; THIEME, Karina; QUEIROZ, Marcia S.; MACHADO, Ubiratan F.; GIANNELLA-NETO, Daniel; PASSARELLI, Marisa; CORREA-GIANNELLA, Maria LuciaQuantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE (AGER) and AGER1 (DDOST)] and of the gene coding the deacetylase SIRT1 (SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming >= 12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.
- Identification and performance of multiple clinical and laboratorial risk factors for diagnosis of cardiac autonomic neuropathy in type 1 diabetes patients(2019) RIGUETTO, Cinthia Minatel; TAKANO, Caroline Rigoleto; ADMONI, Sharon Nina; PARISI, Maria Candida Ribeiro; GIANNELLA, Maria Lucia Correa; PAVIN, Elizabeth Joao; MOURA NETO, ArnaldoPurpose The incidence of cardiac autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D) is frequently underestimated. Individuals with T1D and CAN have an increased mortality risk, mainly from cardiovascular causes. The objectives of the present study were to assess the clinical and laboratory characteristics associated with CAN in patients with T1D and verify the ability of multiple clinical factors to help identify patients with this condition. Methods 102 patients with T1D were evaluated for CAN using standardized cardiovascular reflex testing. Clinical characteristics were used to compute a numerical score for CAN diagnosis and a ROC curve elaborated for assessment of the best cutoff to predict CAN. This score was then applied to the second sample of 120 patients. The sensitivity, specificity, and positive and negative predictive values were calculated. Results Prevalence of CAN was around 35% in the first sample of patients and just below 20% in the second sample. Hypertension, total cholesterol, triglycerides, postprandial sweating, diastolic blood pressure, abnormal right and left 10 g monofilament, retinopathy, and nephropathy were considered independent predictors of CAN. The CAN-score cut-off was 16.88. This yielded a sensitivity of 50%, specificity 73.8%, positive predictive value 22.9%, and negative predictive value 90.5%. Conclusion The use of a subset of clinical and laboratory characteristics can be more accessible than the cardiac reflex tests and more accurate than a single isolated characteristic.
- Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes(2019) SANTOS-BEZERRA, Daniele Pereira; ADMONI, Sharon Nina; MORI, Rosana Cristina; PELAES, Tatiana Souza; PEREZ, Ricardo Vesoni; MACHADO, Cleide Guimaraes; MONTEIRO, Maria Beatriz; PARISI, Maria Candida; PAVIN, Elizabeth Joao; QUEIROZ, Marcia Silva; PASSARELLI, Marisa; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria LuciaAims/Introduction Epigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications. Material and Methods We assessed the frequency of five single-nucleotide polymorphisms in the gene encoding deoxyribonucleic acid methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414 and rs10854076), and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy in 359 individuals with long-term type 1 diabetes. Results None of the single-nucleotide polymorphisms studied was significantly associated with the presence of chronic complications in the overall population. However, after sex stratification, the minor allele C of rs11085721 conferred risk for cardiovascular neuropathy in women after adjustment for confounding variables (odds ratio 2.32; 95% confidence interval 1.26-4.33; P = 0.006). Conclusions The fact that heterozygous mutations in DNMT1 are associated with hereditary sensory autonomic neuropathy provides plausibility to the present finding. If confirmed in independent samples, it suggests that genetic variants in epigenetic genes might predispose to more or fewer epigenetic changes in the face of similar metabolic derangements triggered by hyperglycemia, constituting the ""genetics of epigenetics"" for microvascular diabetes complications.
- Variants inHSD11B1gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes(2021) MORI, Rosana Cristina; SANTOS-BEZERRA, Daniele Pereira; PELAES, Tatiana Souza; ADMONI, Sharon Nina; PEREZ, Ricardo Vessoni; MONTEIRO, Maria Beatriz; MACHADO, Cleide Guimaraes; QUEIROZ, Marcia Silva; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria LuciaBackground and aim 11 beta-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association ofHSD11B1SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. Materials and methods Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). Results The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96;P= .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37;P= .028). A follow-up study revealed that 29% of the individuals lost >= 5 mL min(-1)x 1.73 m(2)per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89;P= .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42;P= .004). Conclusion SNPs in theHSD11B1gene may confer susceptibility to DKD and to IR in T1D individuals.
- Micro-RNAs 518d-3p and 618 Are Upregulated in Individuals With Type 1 Diabetes With Multiple Microvascular Complications(2019) SANTOS-BEZERRA, Daniele P.; SANTOS, Aritania S.; GUIMARAES, Gabriel C.; ADMONI, Sharon N.; V, Ricardo Perez; MACHADO, Cleide G.; PELAES, Tatiana S.; PASSARELLI, Marisa; MACHADO, Ubiratan F.; QUEIROZ, Marcia S.; SILVA, Maria Elizabeth R. da; CORREA-GIANNELLA, Maria LuciaObjective: To compare the serum micro-RNAs (miRNAs) profile of individuals with type 1 diabetes without microvascular complications vs. those with multiple severe microvascular complications, in order to identify epigenetically modulated pathways in these two groups of individuals. Research Design and Methods: A total of 10 subjects were selected among individuals followed in the Diabetes Outpatient Clinic and sorted according to the absence or presence of all microvascular complications. Samples from these participants were used for evaluation of serum miRNA expression profile employing a qRT-PCR assay with hydrolysis probes based on the Taqman Low Density Arrays (TLDA) system. The top six most differentially expressed miRNAs between the aforementioned groups were validated by qRT-PCR in additional 47 type 1 diabetes individuals sorted according to the absence or presence of all microvascular complications and matched for age, sex, degree of metabolic control, diabetes duration, and age at diagnosis. Results: Twenty one out of three hundred and seventy seven miRNAs were upregulated in the group of individuals with all microvascular complications vs. the group without complications. The following miRs were validated: 518-3p, 34a-5p, 126-5p, 425-5p, 618, and 139-5p and logistic regression analyses showed that miRNA-518-3p and miRNA-618 were positively associated with multiple microvascular complications after adjustment for age, sex, diabetes duration, HbA(1)c and use of statin, angiotensin-converting enzyme inhibitors and amlodipine. Conclusions: In this cohort of type 1 diabetes individuals, serum miR-518d-3p and miR-618 were upregulated in those with diabetes kidney disease, diabetes retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy in comparison to individuals with no microvascular complications.
- New digital tool to facilitate subcutaneous insulin therapy orders: an inpatient insulin dose calculator(2015) TOYOSHIMA, Marcos Tadashi Kakitani; SOUZA, Alexandre Barbosa Camara de; ADMONI, Sharon Nina; CUKIER, Priscilla; LOTTENBERG, Simao Augusto; LATRONICO, Ana Claudia; NERY, MarciaBackground: Inpatient hyperglycemia is associated with adverse outcomes in hospitalized patients, with or without known diabetes. The adherence to American College of Endocrinology and American Diabetes Association guidelines recommendations for inpatient glycemic control is still poor, probably because of their complexity and fear of hypoglycemia. Objective: To create software system that can assist health care providers and hospitalists to manage the insulin therapy orders and turn them into a less complicated issue. Methods: A software system was idealized and developed, according to recommendations of major consensus and medical literature. Results: HTML software was developed to be readily accessed from a workstation, tablet or smartphone. Standard initial daily total dose of insulin was 0.4 units/kg and could be modified by distinct factors, such as chronological age, renal and liver function, and high dose corticosteroids use. Insulin therapy consisted of basal, prandial and correction insulin according to nutritional support, glycemic control and outpatient treatment for diabetes. Human insulin or insulin analogues could be options for insulin therapy. Sensitivity factor was based on 1800 Rule for rapid-acting insulin and the 1500 Rule for short-acting insulin. Insulin-naive patients with initial BG level less than 250 mg/dL were considered to have an initial step-wise approach with prandial and correction insulin. The calculator system has allowed insulin dose readjustments periodically, according to daily average blood glucose measurements. Conclusion: We developed software that can be a useful tool for all public hospitals, where generally human insulin is the only available.